Objective:To investigate the differences in gene mutations and functional clusters of gene mutations in patients with myelodysplastic syndromes (MDS) in the lower-risk and higher-risk groups.Methods:A retrospective case series study was conducted. Clinical data of 227 patients with MDS in Zhongda Hospital of Southeast University from January 2018 to August 2023 were retrospectively analyzed. According to the Revised International Prognostic Scoring System (IPSS-R), MDS patients were categorized into the lower-risk group (IPSS-R score ≤3.5 points, 96 cases) and the higher-risk group (IPSS-R score >3.5 points, 131 cases). Bone marrow specimens were tested for mutations of 58 common MDS genes using next-generation sequencing, and the 24 genes with the high mutation rates were included in the study, and the 24 mutated genes were categorized into 8 clusters according to gene function. The differences in clinical data, gene mutations and gene mutation functional clusters were compared between the lower-risk group and the higher-risk group.Results:At least 1 gene mutation was detected in 177 (78.0%) of 227 MDS patients, of which the 5 genes with high mutation rates were ASXL1 [21.6% (49/227)], TET2 [18.5% (42/227)], TP53 [15.4% (35/227)], DNMT3A [13.2% (30/227)], and U2AF1 [10.1% (23/227)] in turn. By gene function analysis, the most common mutation cluster was methylation-related genes [31.3% (71/227)], followed by spliceosome-related genes [24.7% (56/227)]. Platelet count and neutrophil count in the lower-risk group were higher than those in the higher-risk group, and the proportion of bone marrow primitive cells, the mutation rate and the presence of ≥3 mutations were lower than those in the higher-risk group (all P < 0.05). The 5 genes with high mutation rates in the lower-risk group were TET2 [21.9% (21/96)], DNMT3A [14.6% (14/96)], ASXL1 [13.5% (13/96)], SF3B1 [12.5% (12/96)], and U2AF1 [8.3% (8/96)] in turn. The 5 genes with high mutation rates in the higher-risk group were ASXL1 [27.5% (36/131)], TP53 [23.7% (31/131)], TET2 [16.0% (21/131)], DNMT3A [12.2% (16/131)], and U2AF1 [11.5% (15/131)] in turn, and the mutation rates of ASXL1, TP53, ETV6, and NRAS genes in the lower-risk group were lower than those in the higher-risk group (all P < 0.05). The mutation rate of methylation-related genes was the highest in both the lower-risk group and the higher-risk group, but the difference between the two groups was not statistically significant [32.3% (31/96) vs. 30.5% (40/131), χ2 = 0.08, P>0.05]. The differences in the proportions of tumor factor suppressor-related genes, transcription factor-related genes, chromatin-modification-related genes and RAS pathway-related genes mutations between the two groups were all statistically significant (all P < 0.05). Conclusions:The higher-risk group has a higher rate of common gene mutations and a greater number of gene mutations than the lower-risk group in MDS patients.

Objective To observe the differences in the expression levels of the hypoxia-inducible factor-1α/heme oxygenase-1/vascular endothelial growth factor A (HIF-1α/HO-1/VEGF-A) signaling pathway under different maturation outcomes of arteriovenous fistula (AVF) in patients with stage 5 chronic kidney disease, and explore the regulatory mechanism of the HIF-1α/HO-1/VEGF-A signaling pathway in the maturation process of AVF. Methods A total of 45 patients with AVF surgery for stage 5 chronic kidney disease were selected as research objects, vascular specimens were collected during the AVF surgery, and the patients were divided into AVF maturation group (n=35) and AVF poor maturation group (n=10) based on the AVF maturation outcomes within 8 weeks after surgery. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression levels of HIF-1α, HO-1 and VEGF-A in the HIF-1α/HO-1/VEGF-A signaling pathway; the Western blotting was used to detect the protein expression levels of HIF-1α, HO-1 and VEGF-A; the enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of downstream inflammatory factors such as interleukin-1β (IL-1β), interleukin-8 (IL-8), and transforming growth factor-β (TGF-β). Results The expression levels of HIF-1α mRNA, HO-1 mRNA, and VEGF-A mRNA in the AVF maturation group were significantly higher than those in the AVF poor maturation group (P < 0.01); the protein expression levels of HIF-1α, HO-1 and VEGF-A in the AVF maturation group were significantly higher than those in the AVF poor maturation group (P < 0.01); the expression levels of IL-1β, IL-8 and TGF-β in the AVF maturation group were significantly lower than those in the AVF poor maturation group (P < 0.01). Conclusion The upregulation of the HIF-1α/HO-1/VEGF-A signaling pathway is conducive to the early maturation of AVF. The measurement of the expression levels of the HIF-1α/HO-1/VEGF-A signaling pathway has a certain predictive significance for the early maturation outcome of AVF.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective To evaluate the efficacy and safety of Ilaprazole Enteric-Coated Tablets in the treatment of RE. Methods The databases of CNKI, VIP, Wanfang Data, PubMed, Embase, and The Cochrane Library were searched to collect all the randomized controlled trials (RCTs) of Ilaprazole in the treatment of RE published before April 2021. After data extraction and quality evaluation, the RCTs meeting the inclusion criteria were performed, and the meta-analysis was conducted by RevMan 5.4. Results Nine RCTs were included, with a total of 1115 patients of RE. The results of the meta-analysis showed that Ilaprazole Enteric-Coated Tablets were comparable to Esomeprazole Enteric-Coated Tablets in both endoscopic efficiency (90.08% vs. 90.00%, P > 0.05) and symptom relief rates (91.79% vs. 91.23%, P > 0.05), and there was no statistically significant difference in the incidence of adverse reactions (7.99% vs. 8.66%, P > 0.05). Conclusion Ilaprazole Enteric-Coated Tablets with lower doses were comparable to Esomeprazole Enteric-Coated Tablets which showed good efficacy and safety in the treatment of reflux esophagitis.

BackgroundThe incidence of delirium in critically ill psychiatric patients is high， and there are many factors affecting delirium occurrence. At present， epidemiological studies on delirium among critically ill patients in psychiatric hospitals are limited. ObjectiveTo explore the risk factors for delirium in critically ill patients in a psychiatric hospital， so as to guide the clinical management of delirium in psychiatric hospitals. MethodsThis retrospective study included 427 critically ill patients who were admitted to Shenzhen Kangning Hospital from January 1， 2019 to May 31， 2021. The delirium situation， gender， age， pre-admission course of illness （duration from the onset of acute mental state changes to in-patient registration at a psychiatric hospital）， history of mental illness， history of cognitive dysfunction， history of using psychoactive substances， history of using sedative and hypnotic drugs， number of combined chronic diseases， number of combined drugs and type of disease were examined as potential risk factors for delirium. Single Logistic regression was used to analyze the potential risk factors for delirium， and the potential risk factors were incorporated into the multi-factor Logistic regression analysis model so as to gradually screen out the risk factors for delirium in critically ill psychiatric patients. ResultsDelirium was present in 33.49% （143/427） of critically ill patients. Multi-factor Logistic regression analysis demonstrated that the presence of delirium was associated with mental and behavioral disorders caused by psychoactive substances （OR=8.949， P<0.01）， absent history of mental illness （OR=4.202， P<0.01）， number of combined chronic diseases （OR=1.249， P<0.01）， age （OR=1.031， P<0.01） and pre-admission course of illness （OR=0.942， P<0.01） . ConclusionDelirium was present in nearly 1/3 critically ill patients in the psychiatric hospital. The risk factors for delirium included short course of illness before admission， age， more combined chronic diseases， absent history of mental illness， mental and behavioral disorders caused by psychoactive substances. ［Funded by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties （number， SZGSP013）］

Objective:To investigate the diagnosis and treatment of intravascular large B-cell lymphoma (IVLBCL).Methods:The clinical data of 1 patient with adrenal IVLBCL in Zhongda Hospital Southeast University in May 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was an elderly male with recurrent fever of unknown cause at initial stage, and was finally diagnosed as adrenal IVLBCL based on the results of laboratory, imaging and adrenal biopsy at different stages. After multiple courses of R-COP in combination with Bruton tyrosine kinase (BTK) inhibitor, the patient achieved complete remission.Conclusions:IVLBCL is rare and it lacks specific clinical symptoms. PET-CT and pathological biopsy can help in the diagnosis of it. R-COP combined with BTK inhibitor is effective in the treatment of biphenotype IVLBCL.

Rutin,a flavonoid found in fruits and vegetables,is a potential anticancer compound with strong anti-cancer activity.Therefore,electrochemical sensor was developed for the detection of rutin.In this study,CoWO4 nanosheets were synthesized via a hydrothermal method,and porous carbon(PC)was prepared via high-temperature pyrolysis.Successful preparation of the materials was confirmed,and character-ization was performed by transmission electron microscopy,scanning electron microscopy,and X-ray photoelectron spectroscopy.A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin.The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability.PC has a high surface-to-volume ratio and superior conductivity.Moreover,the hydrophobicity of PC allows large amounts of rutin to be adsorbed,thereby increasing the concentration of rutin at the electrode surface.Owing to the syn-ergistic effect of the 3D CoWO4 nanosheets and PC,the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity.The sensor showed a good linear range(5-5000 ng/mL)with a detection limit of O.45 ng/mL.The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

OBJECTIVE: To investigate the effect and mechanism of artesunate (ARTS) combined with cytarabine(Ara-C) and/or daunorubicin (DNR) on the proliferation and apoptosis of MV4-11 human mixed-lineage leukemia rearranged（MLL-r） acute myeloid leukemia (AML) cell line. METHODS: CCK-8 assay was used to detect the proliferation effect of individual or in combination of ARTS, DNR, Ara-C on MV4-11 cells. The IC₅₀ of ARTS, DNR and Ara-C was calculated separately. The cell apoptosis and expression of receptors DR4 and DR5 were detected by flow cytometry. Western blot was used to detect the expression of Caspase-3 and Caspase-9 in each groups. RESULTS: The inhibition effect of ARTS, Ara-C and DNR on the proliferation of MV4-11 were all dose-dependently (r=0.99, 0.90 and 0.97, respectively). The IC₅₀ of ARTS, Ara-C and DNR on MV4-11 for 48 hours were 0.31 μg/ml, 1.43 μmol/L and 22.47 nmol/L, respectively. At the dose of ARTS 0.3 μg/ml， Ara-C 1.0 μmol/L and DNR 15 nmol/L, the proliferation rate for 48 hours of the tri-combination treatment was significantly lower than that of the bi-combination treatment, while both were significantly lower than that of the individual treatment (all P＜0.05). In terms of bi-combination treatment, the cells proliferation rate for 48 hours of the ARTS+Ara-C group was significantly lower than that of the ARTS+DNR group, while both were significantly lower than that of the Ara-C+DNR group (all P＜0.05). The cooperativity index (CI) of bi- and tri-combination treatment were all less than 1. After 48 hours of drug action, the cell apoptosis rate of the ARTS+DNR+Ara-C group was significantly higher than that of the Ara-C+DNR group, while both were significantly higher than that of the ARTS+DNR group (all P＜0.05). Meanwhile, the was no statistical difference between the cells apoptotic rate of the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (P>0.05). The expression of DR4 and DR5 also showed no difference between control group and drug group. Compared with the DNR+Ara-C group, the expressions of Caspase-3 were significantly down-regulated in both the ARTS+DNR+Ara-C group and the ARTS+Ara-C group (all P＜0.05). The down-regulation of Caspase-3 expression was the most significantly in the combination group of three drugs, while the Caspase-9 expressions in different groups showed no apparent change. CONCLUSION The in vitro study showed that tri-combination of ARTS+Ara-C+DNR and bi-combination of ARTS+Ara-C could inhibit the proliferation and promote apoptosis of MV4-11 cell line. The inhibition effect of these two combinations were significantly superior to that of the traditional Ara-C+DNR treatment. The mechanism underlying this finding may be identified by the down regulation of Caspase-3, while no altered expression was observed of Caspase-9, DR4 and DR5.
Humans ; Cytarabine/pharmacology* ; Daunorubicin/pharmacology* ; Caspase 3 ; Caspase 9 ; Artesunate/pharmacology* ; Leukemia, Myeloid, Acute ; Apoptosis ; Cell Line

Yuebawei refers to 8 kinds of genuine medicinal materials in south China area，namely Citri Grandis Exocarpium， Citrus reticulata， Amomum villosum， Pogostemon cablin， Morinda officinalis， Aquilaria sinensis， Citrus medica and Polygonum multiflorum. The results of this review show that， the pharmacological effects of Yuebawei are very extensive. It has significant effects in relieving cough and phlegm， anti-bacterial and anti-inflammatory， enhancing immunity， anti-oxidation， antidepressant， immune regulation and regulating gastrointestinal function. Its development and application prospects are broad， but most of the existing pharmacological studies stay on pharmacodynamic studies. In the aspect of the safety research of Yuebawei， there are few studies on the safety of other medicinal materials， except for the liver toxicity of P. multiflorum； at the same time， there are few comparative studies on the therapeutic advantages of Yuebawei and other local medicinal materials in clinical application. It is necessary to strengthen the research on the material basis of pharmacological action mechanism， and safety and efficacy observation of clinical medication for Yuebawei， so as to provide scientific basis for the development of new drugs and clinical promotion and application of Yuebawei.

Objective:To investigate the characteristics of implicit memory and its related factors in schizophrenic patients with negative and positive symptoms.Methods:Ninety-three schizophrenic patients (including 52 cases of negative symptoms group and 41 cases of positive symptoms group) and 30 normal controls (normal group) were tested with the method of Chinese character word completion method. The reaction time and correct rate were recorded and compared with analysis of variance and t-test, and the correlation with demographic factors was analyzed with Pearson correlation analysis. Results:Accuracy of implicit memory test in schizophrenia group: there were statistically significant differences in the accuracy of patients with different course of disease (≤5 years: (38±5)%, 5-15 years: (34±8)%, ≥15 years: (34±7)%, P<0.05).The differences were statistically significant in the accuracy of patients with different education levels(primary school: (35±6)%, junior and senior high school: (34±7)%, secondary college education and above: (39±5)%, P<0.05).The accuracy of patients with education years < 10 years ((34±7)%) was significantly lower than those with education years ≥10 years ((37±6)%, P<0.05).Reaction time results of implicit memory test in schizophrenia group : there were significant differences in reaction time of patients with different disease course(≤5 years: (3 248±971)ms, 5-15 years: (3 515±672)ms, ≥15 years: (3 925±842)ms, P<0.05).The differences were statistically significant in the reaction time of workers ((3 495±712)ms), farmers ((3 870±878)ms) and soldiers ((3 024±924)ms, P<0.05).The reaction time of patients with clozapine ((3 869±871)ms) was significantly higher than that of patients with olanzapine ((3 393±626)ms, P<0.05).Intergroup results of accuracy: the accuracy of normal control group ((40±5)%) was significantly higher than that of negative symptom group ((33±7)%, P<0.01).The accuracy of negative symptom group was significantly lower than that of positive symptom group ((37±6)%, P<0.01).Intergroup reaction time results: the reaction time of normal control group ((2 660±667)ms) was significantly lower than that of negative symptom group ((3 678±951)ms, P<0.01) and positive symptom group ((3 072±865)ms, P<0.05).The reaction time of negative symptom group ((3 678±951)ms)was significantly higher than that of positive symptom group( P<0.01).There was significant negative correlation between the accuracy of implicit memory and the course of disease in schizophrenia ( r=-0.22, P<0.05). Conclusion:The implicit memory of schizophrenic patients is related to the course of disease, taking drugs, and occupation.There may have differences in implicit memory between patients with negative and positive symptoms of schizophrenia.